The glycolytic pathway is a ten-step series of reactions that forms the major metabolic pathway in nearly all organisms. Flux through the glycolytic pathway is adjusted in response to conditions both inside and outside the cell. Irreversible glycolytic reactions are those catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase. In metabolic pathways, such enzymes are potential targets for control, and all three enzymes serve this purpose in glycolysis. The PFKFB enzymes (PFKFB 1-4) synthesize fructose-2,6-bisphosphate (F2,6BP) which activates 6-phosphofructo-1-kinase (PFK-1), an essential control point in the glycolytic pathway.
Neoplastic cells preferentially utilize glycolysis to satisfy their increased needs for energy and biosynthetic precursors. Malignant tumor cells have glycolytic rates that are up to 200 times higher than those of their normal tissues of origin. One cancer attack strategy has been to treat cancer by starving cancerous cells in various ways. Reducing or blocking the enhanced glycolytic flux mechanism present in cancer cells has stimulated recent interest.
Despite greater understanding and pharmaceutical advances in the diagnosis and treatment of cancer, it is still estimated that nearly 13% of all human deaths last year were due to cancer. Thus, there remains a need for safe and effective anti-cancer therapeutics, particularly those which target neoplastic cells via mechanisms such as glycolytic flux, which are over-expressed in cancer cells.